WO2013016668A3 - Methylphenidate-prodrugs, processes of making and using the same - Google Patents

Methylphenidate-prodrugs, processes of making and using the same Download PDF

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Publication number
WO2013016668A3
WO2013016668A3 PCT/US2012/048641 US2012048641W WO2013016668A3 WO 2013016668 A3 WO2013016668 A3 WO 2013016668A3 US 2012048641 W US2012048641 W US 2012048641W WO 2013016668 A3 WO2013016668 A3 WO 2013016668A3
Authority
WO
WIPO (PCT)
Prior art keywords
methylphenidate
prodrugs
derivatives
processes
making
Prior art date
Application number
PCT/US2012/048641
Other languages
French (fr)
Other versions
WO2013016668A2 (en
Inventor
Sven Guenther
Guochen Chi
Bindu Bera
Travis Mickle
Original Assignee
Kempharm Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU2012286683A priority Critical patent/AU2012286683C1/en
Priority to EP12817423.2A priority patent/EP2736510B1/en
Priority to KR1020167010571A priority patent/KR101869885B1/en
Priority to RU2014107678/04A priority patent/RU2573835C2/en
Priority to KR1020197020055A priority patent/KR20190085184A/en
Priority to KR1020187017033A priority patent/KR20180069934A/en
Priority to LTEP12817423.2T priority patent/LT2736510T/en
Priority to DK12817423.2T priority patent/DK2736510T3/en
Priority to ES12817423.2T priority patent/ES2621306T3/en
Priority to KR1020137034565A priority patent/KR101616111B1/en
Priority to MX2016010664A priority patent/MX362571B/en
Priority to BR112014002084-1A priority patent/BR112014002084B1/en
Priority to NZ618113A priority patent/NZ618113B2/en
Priority to CN201280037735.0A priority patent/CN103826633B/en
Priority to JP2014523083A priority patent/JP5976111B2/en
Priority to SI201230904A priority patent/SI2736510T1/en
Priority to RS20170338A priority patent/RS55812B1/en
Application filed by Kempharm Inc. filed Critical Kempharm Inc.
Priority to KR1020197020054A priority patent/KR20190085183A/en
Priority to US14/234,440 priority patent/US9079928B2/en
Priority to MX2013015088A priority patent/MX341416B/en
Priority to EP17157635.8A priority patent/EP3189840B1/en
Priority to CA2837732A priority patent/CA2837732C/en
Priority to UAA201402019A priority patent/UA112654C2/en
Publication of WO2013016668A2 publication Critical patent/WO2013016668A2/en
Publication of WO2013016668A3 publication Critical patent/WO2013016668A3/en
Priority to ZA2013/08766A priority patent/ZA201308766B/en
Priority to IL230650A priority patent/IL230650A/en
Priority to US14/727,498 priority patent/US9453037B2/en
Priority to IL246503A priority patent/IL246503A/en
Priority to US15/249,088 priority patent/US10231960B2/en
Priority to HRP20170555TT priority patent/HRP20170555T1/en
Priority to IL254143A priority patent/IL254143B/en
Priority to IL26249318A priority patent/IL262493B/en
Priority to US16/244,460 priority patent/US20190142815A1/en
Priority to IL269322A priority patent/IL269322B/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/59—Hydrogenated pyridine rings
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    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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    • C07K5/06—Dipeptides
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    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala

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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Genetics & Genomics (AREA)
  • Psychiatry (AREA)
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  • Nutrition Science (AREA)
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  • Hematology (AREA)
  • Obesity (AREA)
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  • Heart & Thoracic Surgery (AREA)
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  • Pain & Pain Management (AREA)
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Abstract

The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof.
PCT/US2012/048641 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same WO2013016668A2 (en)

Priority Applications (33)

Application Number Priority Date Filing Date Title
KR1020197020054A KR20190085183A (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
RS20170338A RS55812B1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
EP12817423.2A EP2736510B1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
KR1020197020055A KR20190085184A (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
KR1020187017033A KR20180069934A (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
LTEP12817423.2T LT2736510T (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
DK12817423.2T DK2736510T3 (en) 2011-07-28 2012-07-27 METHYLPHENIDATE PRODRUGS, PROCEDURES FOR PREPARING IT AND USING THE SAME
ES12817423.2T ES2621306T3 (en) 2011-07-28 2012-07-27 Prodrugs of methylphenidate, processes for obtaining and using them
KR1020137034565A KR101616111B1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
MX2016010664A MX362571B (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same.
BR112014002084-1A BR112014002084B1 (en) 2011-07-28 2012-07-27 Prodrug composition and use of methylphenidate conjugate
NZ618113A NZ618113B2 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
CN201280037735.0A CN103826633B (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
JP2014523083A JP5976111B2 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrug, its production and use
SI201230904A SI2736510T1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
KR1020167010571A KR101869885B1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
RU2014107678/04A RU2573835C2 (en) 2011-07-28 2012-07-27 Methylphenidate prodrugs, methods of their obtaining and application
AU2012286683A AU2012286683C1 (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same
US14/234,440 US9079928B2 (en) 2011-07-28 2012-07-27 Methylphenidate-oxoacid conjugates, processes of making and using the same
MX2013015088A MX341416B (en) 2011-07-28 2012-07-27 Methylphenidate-prodrugs, processes of making and using the same.
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Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101616111B1 (en) 2011-07-28 2016-04-27 켐팜 인코포레이티드 Methylphenidate-prodrugs, processes of making and using the same
ES2715562T3 (en) * 2011-12-15 2019-06-04 Alkermes Pharma Ireland Ltd Prodrugs of secondary amine compounds
US9556156B2 (en) * 2012-10-05 2017-01-31 Sphaera Pharma Pte Ltd. Compounds, their synthesis and their uses
WO2015001499A2 (en) * 2013-07-04 2015-01-08 Mahesh Kandula Compositions and methods for the treatment of irritable bowel syndrome and the associated abdominal cramping
CN104418797B (en) * 2013-08-26 2019-04-19 上海医药集团股份有限公司 Methylphenidate, the preparation method of dexmethylphenidate, wherein mesosome and preparation method
US20170056352A1 (en) 2015-08-25 2017-03-02 Rgenix, Inc. PHARMACEUTICALLY ACCEPTABLE SALTS OF beta-GUANIDINOPROPIONIC ACID WITH IMPROVED PROPERTIES AND USES THEREOF
WO2017048720A1 (en) * 2015-09-15 2017-03-23 Praxis Biosciences, Llc Prodrugs of fencamfamine
CA3041058A1 (en) 2016-10-31 2018-05-03 Biocryst Pharmaceuticals, Inc. Carbamimidoylphenylcarbamoyl derivatives and pharmaceutical compositions thereof useful as kallikrein inhibithors
NZ754751A (en) * 2016-12-11 2022-05-27 Kempharm Inc Compositions comprising methylphenidate-prodrugs, processes of making and using the same
WO2018107131A1 (en) * 2016-12-11 2018-06-14 Kempharm, Inc. Methylphenidate-prodrugs, processes of making and using the same
WO2018160178A1 (en) 2017-03-01 2018-09-07 Rgenix, Inc. Pharmaceutically acceptable salts of b-guanidinopropionic acid with improved properties and uses thereof
US20200114014A1 (en) * 2017-04-11 2020-04-16 John K. Thottathil Novel Alpha-Hydroxy Carboxylic Acid and Derivatives and Other GRAS-Based Amide and Imide Prodrugs of Amphetamine Compounds and Uses Thereof
US11975039B2 (en) 2018-05-10 2024-05-07 Helixmith Co., Ltd. Herbal composition for treatment of attention deficit hyperactivity disorder
JPWO2020067507A1 (en) * 2018-09-28 2021-08-30 生化学工業株式会社 Primary amine compound or secondary amine compound-acidic polysaccharide conjugate and its production method
US11174229B2 (en) * 2018-10-29 2021-11-16 Kempharm, Inc. D-amphetamine compounds, compositions, and processes for making and using the same
WO2023230205A1 (en) 2022-05-25 2023-11-30 Ikena Oncology, Inc. Mek inhibitors and uses thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999036403A1 (en) * 1998-01-13 1999-07-22 The Trustees Of The University Of Pennsylvania Novel dopamine re-uptake inhibitors and methods of synthesizing and using the same
US6210705B1 (en) * 1997-12-15 2001-04-03 Noven Pharmaceuticals, Nc. Compositions and methods for treatment of attention deficit disorder and attention deficit/hyperactivity disorder with methylphenidate
US20060100243A1 (en) * 2004-10-22 2006-05-11 Mark Froimowitz Methylphenidate analogs and methods of use thereof
US20100145057A1 (en) * 2007-03-15 2010-06-10 Sun Pharma Advanced Research Company Ltd. Novel prodrugs

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4428935A (en) * 1982-05-24 1984-01-31 Pfizer Inc. Penicillanic acid dioxide prodrug
US7060708B2 (en) * 1999-03-10 2006-06-13 New River Pharmaceuticals Inc. Active agent delivery systems and methods for protecting and administering active agents
WO2001054481A2 (en) * 2000-01-28 2001-08-02 Rohm And Haas Company Enhanced propertied pharmaceuticals
JP2004507503A (en) * 2000-08-28 2004-03-11 センション，インコーポレイテッド Use of threo-methylphenidate to enhance memory
US20020132793A1 (en) * 2000-08-28 2002-09-19 Mel Epstein Use of methylphenidate compounds to enhance memory
US7700561B2 (en) 2002-02-22 2010-04-20 Shire Llc Abuse-resistant amphetamine prodrugs
WO2004080959A2 (en) * 2003-03-07 2004-09-23 Isp Investments Inc. Process for the preparation of dexmethylphenidate hydrochloride
FI120187B (en) * 2003-03-14 2009-07-31 Outotec Oyj A method for controlling the process
EP1928881A2 (en) 2005-08-19 2008-06-11 Pharmacofore, Inc. Prodrugs of active agents
KR20090086627A (en) * 2006-12-05 2009-08-13 노이로제스엑스, 인코포레이티드 Prodrugs and methods of making and using the same
EP2101571B1 (en) * 2006-12-11 2011-05-18 Kempharm, Inc. Ornithine conjugates of amphetamine and processes for making and using the same
CN101631770A (en) * 2007-02-02 2010-01-20 科露西德医药品公司 The compound that suppresses Pseudocholinesterase
MX2009008288A (en) * 2007-02-02 2009-12-01 Colucid Pharmaceuticals Inc Compounds that inhibit cholinesterase.
AU2008213643A1 (en) * 2007-02-08 2008-08-14 Kempharm, Inc. Polar hydrophilic prodrugs of amphetamine and other stimulants and processes for making and using the same
DK2152690T3 (en) * 2007-05-23 2012-05-07 Merck Sharp & Dohme Pyridylpiperidinorexin receptor antagonists
EP2182938A2 (en) * 2007-07-18 2010-05-12 Colucid Pharmaceuticals, Inc. Methods for promoting wakefulness
WO2009035473A2 (en) 2007-09-13 2009-03-19 Sanfilippo Louis C Method of treating binge eating disorder, obesity resulting from binge eating behavior and depressive disorders
KR101616111B1 (en) * 2011-07-28 2016-04-27 켐팜 인코포레이티드 Methylphenidate-prodrugs, processes of making and using the same
ES2715562T3 (en) 2011-12-15 2019-06-04 Alkermes Pharma Ireland Ltd Prodrugs of secondary amine compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6210705B1 (en) * 1997-12-15 2001-04-03 Noven Pharmaceuticals, Nc. Compositions and methods for treatment of attention deficit disorder and attention deficit/hyperactivity disorder with methylphenidate
WO1999036403A1 (en) * 1998-01-13 1999-07-22 The Trustees Of The University Of Pennsylvania Novel dopamine re-uptake inhibitors and methods of synthesizing and using the same
US20060100243A1 (en) * 2004-10-22 2006-05-11 Mark Froimowitz Methylphenidate analogs and methods of use thereof
US20100145057A1 (en) * 2007-03-15 2010-06-10 Sun Pharma Advanced Research Company Ltd. Novel prodrugs

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PILLI ET AL.: "The Stereochemistry of the Addition of Chlorotitanium Enolates of N-Acyl Oxazolidin-2-ones to 5- and 6- Membered N-Acyliminium Ions", J. BRAZ. CHEM. SOC., vol. 12, no. 5, 2001, pages 634 - 651, XP055137254 *

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